We propose to conduct a first-ever comprehensive quantitative investigation of motor function in autism using simultaneous brain and movement imaging. A novel system developed by Co- Investigator Makeig and his colleagues (Mobile Brain/Body Imaging, MoBI), will allow us to measure timing, accuracy and efficiency of natural full body motion during self-initiated and directed movement while simultaneously recording high density EEG. We will test 25 ASD adolescents (aged 12-16) and 25 typically developing age- and IQ-matched controls. Participants will complete a series of neuropsychological tests, functional assessments, MR and Diffusion Tensor Imaging and MoBI brain and movement imaging. An additional 10 low-functioning young children with autism (aged 4-8) who evidence frequent episodes of repetitive, stereotyped movements will participate in brain and movement imaging during stereotypies. The objective of this exploratory R21 project is to develop and refine data collection and analytic methods for use with ASD individuals in order to: (1) specify the nature of abnormalities of motor function in adolescents with autism or Asperger's disorder;(2) identify the associated underlying brain networks that support motor anticipation, planning and execution in ASD and in typically developing controls;(3) investigate the association of motor dysfunction with other cognitive (e.g., dyspraxia, visual-motor integration) and social symptoms of ASD;and (4) examine motor function and brain activation during repetitive and stereotyped movements in a small sample of low functioning children with autism. Relevance: The recognition that motor dysfunction is a prominent feature in ASD and that these problems may even be a contributing factor in some cognitive and social deficits has led to a variety of interventions featuring motor or sensory-motor training. However, because little is known about the specific nature of motor dysfunction in ASD, these therapies have little scientific guidance. Specific abnormalities and severity of motor symptoms vary from individual to individual, and there is currently no accepted model for organizing this variability or forming sub-types based on patterns of motor dysfunction. Moreover, because of problems inherent in imaging motion, little is known about brain function underlying motor symptoms. The proposed study will address these issues. The study goal is to provide an initial exploration of patterns of motor and associated brain function that may be used to organize the variability in ASD motor dysfunction, and an exploration of the association of motor dysfunction with other cognitive and social symptoms. Methods and data from this exploratory study will also provide the base for a large sample study from which explanatory models can be tested. Isolating specific underlying mechanisms that lead to a variety of motor impairments (e.g., timing, anticipation) would inform effective intervention that may in turn improve not only motor competence but also behavioral problems that are affected by motor dysfunction. PUBLIC HEALTH RELEVANCE: Problems with motor function are prominent in autism, but may differ greatly from person to person. While motor problems can clearly affect daily function, they may also affect social function and may contribute to difficulty learning social skills during early childhood. Our novel system for imaging natural movement and brain activity at the same time will allow us to identify underlying similarities across different impaired movements which will increase our understanding of the nature of motor behavior in ASD and will guide development of effective intervention.